关键词:

Abstract:

Objective To investigate the function of RGFP966，a highly selective histone deacetylase 3 （HDAC3）inhibitor，in radiation ⁃induced neuroinflammation and neuronal injury. Methods Microglia cell line BV2 or hippocampal neuron cell line HT22 were radiated by a medical linear accelerator. The expression of microg⁃ lia activation indicator IBA⁃1 was observed by cellular immunofluorescence；the expression and secretion level of inflammatory cytokines in radiated microglia were detected by quantitative real ⁃ time reverse transcription polymerase chain reaction（qRT⁃PCR）or enzyme⁃linked immunosorbent assay（Elisa）；the activity of BV2 cells and HT22 cells were detected by cell counting kit⁃8 assay；neuronal apoptosis was identified using TUNEL staining. Results RGFP966 dramatically reduced the secretion of inflammatory cytokines brought about by ionizing radiation（IR）in BV2 cells，including tumor necrosis factor α（TNF⁃α），interleukin 6（IL⁃6），and interleukin 1β（IL⁃1β）. Pretreated with RGFP966 significantly reduced the number of apoptosis in radiated HT22 cells. Radia⁃ tion⁃induced impairment of the viability of BV2 cells and HT22 cells was also alleviated by RGFP966. In the mouse model of RBI，RGFP966 significantly reduced the number of neuronal apoptosis. Conclusion The selective HDAC3 inhibitor RGFP966 effectively alleviated microglial neuroinflammation and neuronal apoptosis caused by IR. Therefore，RGFP966 has the potential to treat radiation⁃induced brain injury.

Key words: ionizing radiation, radiation?induced brain injury, HDAC3 inhibitor